Using insulin as a model, the following questions concerning protein hormone actions will be explored: 1. What is the structural basis of the various biological actions of the molecule? 2. What are the mechanisms that control insulin secretion? 3. What is the mechanism by which a protein hormone that has the potential for multiple actions can exert a specific action in a particular physiological situation? 4. What are the changes in the pattern of insulin secretion and action that occur in various disease states? 5. Are there any disease states that are caused by the secretion of structurally altered protein hormones? These questions will be answered using a variety of experimental animal models and certain human disease states. Additionally, studies will be carried out to determine the mechanism of action of serum sulfation factor on cartilage. The model used will be embryonic chicken cartilage.